Influence of FASL and FAS polymorphisms, enrolled in extrinsic apoptosis pathway, in the inherited increased risk of head and neck squamous cell carcinoma

Objectives There are well-established outcome disparities among different demographic groups with head and neck squamous cell carcinoma (HNSCC). We aimed to investigate the potential contribution of patient choice of nonsurgical treatment to these disparities by estimating the rate of this phenomenon, identifying its predictors, and estimating the effect on cancer-specific survival. Study Design Retrospective nationwide analysis. Settings Surveillance, Epidemiology, and End Results Database (2004-2014). Subjects and Methods Patients with HNSCC, who were recommended for primary surgery, were included. Multivariable logistic regression was used to identify demographic and clinical factors associated with patient choice of nonsurgical treatment, and Kaplan Meier/Cox regression was used to analyze survival. Results Of 114,506 patients with HNSCC, 58,816 (51.4%) were recommended for primary surgery, and of those, 1550 (2.7%) chose nonsurgical treatment. Those who chose nonsurgical treatment were more likely to be older (67.1 ± 12.6 vs 63.6 ± 13.1, P < .01), were of Black (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.28-1.74) or Asian (OR = 1.79; 95% CI, 1.46-2.20) ethnicity, were unmarried (OR married, 0.50; 95% CI, 0.44-0.58), had an advanced tumor, and had a hypopharyngeal or laryngeal primary. Choice of nonsurgical treatment imparted a 2.16-fold (95% CI, 2.02-2.30) increased risk of cancer-specific death. Conclusion Of the patients, 2.7% chose nonsurgical treatment despite a provider recommendation that impairs survival. Choice of nonsurgical treatment is associated with older age, having Black or Asian ethnicity, being unmarried, having an advanced stage tumor, and having a primary site in the hypopharynx or larynx. Knowledge of these disparities may help providers counsel patients and help patients make informed decisions.

Download Full-text

Molecular Markers in Head and Neck Squamous Cell Carcinoma: Their Biological Function and Prognostic Significance

Annals of Otology Rhinology & Laryngology ◽

10.1177/000348940111000304 ◽

2001 ◽

Vol 110 (3) ◽

pp. 221-228 ◽

Cited By ~ 16

Author(s):

Benjamin D. Smith ◽

Bruce G. Haffty ◽

Clarence T. Sasaki

Keyword(s):

Squamous Cell Carcinoma ◽

Molecular Markers ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Biological Function ◽

Prognostic Significance ◽

Growth Factor Receptor ◽

Neck Squamous Cell Carcinoma ◽

Increased Risk

Head and neck squamous cell carcinoma affects more than 500,000 people worldwide each year. Despite optimal treatment with surgery, irradiation, and chemotherapy, disease recurrence and progression remains a common and challenging oncological problem. Recently, interest has developed in identifying novel molecular markers that allow identification of those patients at increased risk for locoregional recurrence and death. This article reviews several such molecular markers studied in head and neck cancer, including p53, angiogenesis-related markers, cyclin D1, and epidermal growth factor receptor. The biological function of these markers and the potential clinical implications are discussed. The purpose of this review is to update the otolaryngologist on a rapidly emerging segment of applied translational research in our field.

Download Full-text

FAS and FASL variations in outcomes of tobacco- and alcohol-related head and neck squamous cell carcinoma patients

Tumor Biology ◽

10.1177/1010428320938494 ◽

2020 ◽

Vol 42 (7) ◽

pp. 101042832093849

Author(s):

Ericka Francislaine Dias Costa ◽

Tathiane Regine Penna Lima ◽

Leisa Lopes-Aguiar ◽

Guilherme Augusto Silva Nogueira ◽

Marília Berlofa Visacri ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Multiple Logistic Regression Analysis ◽

Neck Squamous Cell Carcinoma ◽

Response To Treatment ◽

Single Nucleotide Variants ◽

Single Nucleotide ◽

Apoptosis Pathway

Radiotherapy and cisplatin lead to cell killing in head and neck squamous cell carcinoma patients, but adverse events and response to treatment are not the same in patients with similar clinicopathological aspects. The aim of this prospective study was to evaluate the roles of TP53 c.215G > C, FAS c.-671A > G, FAS c.-1378G > A, FASL c.-844 C > T, CASP3 c.-1191A > G, and CASP3 c.-182-247G > T single nucleotide variants in toxicity, response rate, and survival of cisplatin chemoradiation-treated head and neck squamous cell carcinoma patients. Genomic DNA was analyzed by polymerase chain reaction for genotyping. Differences between groups of patients were analyzed by chi-square test or Fisher’s exact test, multiple logistic regression analysis, and Cox hazards model. One hundred nine patients with head and neck squamous cell carcinoma were enrolled in study. All patients were smokers and/or alcoholics. Patients with FAS c.-671GG genotype, FAS c.-671AG or GG genotype, and FASL c.-844CC genotype had 5.52 (95% confidence interval (CI): 1.42–21.43), 4.03 (95% CI: 1.51–10.79), and 5.77 (95% CI: 1.23–27.04) more chances of presenting chemoradiation-related anemia of grades 2–4, lymphopenia of grade 3 or 4, and ototoxicity of all grades, respectively, than those with the remaining genotypes. FAS c.-671GG genotype was also seen as an independent predictor of shorter event-free survival (hazard ratio (HR): 2.05; P = 0.007) and overall survival (HR: 1.83; P = 0.02) in our head and neck squamous cell carcinoma patients. These findings present, for the first time, preliminary evidence that inherited abnormalities in apoptosis pathway, related to FAS c.-671A > G and FASL c.-844 C > T single nucleotide variants, can alter toxicity and survival of tobacco- and alcohol-related head and neck squamous cell carcinoma patients homogeneously treated with cisplatin chemoradiation.

Download Full-text

Abstract 2954: Overexpression of specific genes in surgical margins of head and neck squamous cell carcinoma patients may predict a significantly increased risk of recurrence

10.1158/1538-7445.am10-2954 ◽

2010 ◽

Author(s):

Ana Carolina de Carvalho ◽

André L. Carvalho ◽

Fernando A. Soares ◽

Luiz Paulo Kowalski ◽

Danielle C C Maia ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Surgical Margins ◽

Neck Squamous Cell Carcinoma ◽

Risk Of Recurrence ◽

Increased Risk

Download Full-text

Screening for distress, related problems and perceived need for psycho-oncological support in head and neck squamous cell carcinoma (HNSCC) patients: a retrospective cohort study

BMC Cancer ◽

10.1186/s12885-021-08236-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

V. Kunz ◽

G. Wichmann ◽

A. Lehmann-Laue ◽

A. Mehnert-Theuerkauf ◽

A. Dietz ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Well Being ◽

Distress Thermometer ◽

Neck Squamous Cell Carcinoma ◽

Problem List ◽

Care Needs ◽

Increased Risk

Abstract Background In different cancer entities, several studies have shown the adverse effects of cancer on mental health, psychological well-being and the increased risk of high emotional distress in cancer patients. This study aims to analyze psychosocial distress levels and their relationship between sociodemographic parameters and selected items on the Distress Thermometer (DT) Problem List in head and neck squamous cell carcinoma (HNSCC) patients. Patients and methods We assessed a total of 120 HNSCC patients using the Distress Thermometer (DT) Problem List. Distress scores (DTS) of 90 patients were available. A DTS of ≥ 5 on the visual analogue scale represents clinically relevant distress. Data analysis consisted of descriptive statistics, comparison of mean values for different DTS subcategories and correlation between DTS scores and parameters of tumor classification, sociodemographic variables and selected problems. Results Distress was present in 57.7% of the sample, with a total of 52 patients with a DTS ≥ 5. The mean DTS was 4.7 (SD 2.4). Patients with newly diagnosed HNSCC had significantly higher DTS. Distress levels were significantly associated with sadness, general worries, anxiety, nervousness, sleeping disorders, mouth sores and fever. Out of the total sample, 6 patients and out of these 6 individuals, 5 patients with a DTS ≥ 5 requested referrals to psycho-oncological service. Conclusion High distress levels were common in HNSCC patients but only few patients desired psycho-oncological care. Addressing patients’ supportive care needs in routine clinical practice is essential to meet unmet needs of HNSCC patients and thus improve cancer care.

Download Full-text

Association of Inflammation-Related Gene Polymorphisms With Susceptibility and Radiotherapy Sensitivity in Head and Neck Squamous Cell Carcinoma Patients in Northeast China

Frontiers in Oncology ◽

10.3389/fonc.2021.651632 ◽

2021 ◽

Vol 11 ◽

Author(s):

Ying Li ◽

Li Zhu ◽

Hongmin Yao ◽

Ye Zhang ◽

Xiangyu Kong ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Gene Polymorphisms ◽

Neck Squamous Cell Carcinoma ◽

Interleukin 4 ◽

Related Gene ◽

Dominance Model ◽

Increased Risk

BackgroundInflammation-related gene polymorphisms are some of the most important determinants for cancer susceptibility, clinical phenotype diversity, and the response to radiotherapy and chemotherapy. However, the relationship between these polymorphisms and head and neck squamous cell carcinoma (HNSCC) remains unclear. The aim of this study was to investigate the role of inflammation-related gene polymorphisms in the developmental risk and radiotherapy sensitivity of HNSCC.MethodsThe Matrix-Assisted Laser Desorption Ionization Time of Flight (MALDI-TOF) genotyping system was used to genotype 612 individuals from a Chinese population for 28 inflammation-related gene polymorphisms.ResultsThe protein kinase B (AKT1) rs1130233 TT, dominance model (CT+TT vs. CC), recessive model (TT vs. CT+CC), and rs2494732 CC genotypes were associated with reduced risk of HNSCC (P=0.014; P=0.041; P=0.043). The polymeric immunoglobulin receptor (PIGR) rs291097 GA, dominance model (GA+AA vs. GG), and rs291102 dominance model (GA+AA vs. GG) were associated with increased risk of HNSCC (P=0.025; P=0.025; P=0.040). The interleukin-4 receptor-α (IL-4RA) rs1801275 AA genotype was significantly correlated with increased radiotherapy sensitivity of HNSCC patients (P=0.030). In addition, age ≤ 60 years, non-smoker status, and normal levels of squamous cell carcinoma antigen (SCC) were found to be associated with increased radiotherapy sensitivity of HNSCC patients (P=0.033; P=0.033; P=0.030).ConclusionThe AKT1 rs1130233, AKT1 rs2494732, PIGR rs291097, and PIGR rs291102 polymorphisms were significantly related to the risk of HNSCC. The IL-4RA rs1801275 polymorphism, age ≤ 60 years, non-smoker status, and normal levels of SCC were significantly associated with increased radiotherapy sensitivity of HNSCC.

Download Full-text

The genetic variants of LINC-PINT are related to head and neck squamous cell carcinoma susceptibility in Chinese population

10.21203/rs.3.rs-379009/v1 ◽

2021 ◽

Author(s):

Jincai Xue ◽

Fang Dong ◽

Tianchang Wang ◽

Qinjiang Liu ◽

Jun Wang ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Case Control Study ◽

Neck Squamous Cell Carcinoma ◽

Increased Risk ◽

The Relationship ◽

Control Study ◽

Increased Susceptibility

Abstract Background: Head and neck squamous cell carcinoma (HNSCC) is the most leading incident tumor worldwide. Genetic factors act crucial role in the HNSCC progression. Our study is intent to explore the correlation of LINC-PINT polymorphism with the risk of HNSCC in Chinese population.Methods: The case-control study (including 537 HNSCC cases and 533 controls) was performed to determine the relationship between LINC-PINT polymorphisms and HNSCC susceptibility. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to determine the associations.Results: The current study indicated that rs157916 and rs7781295 in the LINC-PINT gene have a strong significant correlation with HNSCC risk (OR 1.32, p = 0.042; OR 1.31, p = 0.016). Stratification analyses showed that rs157916 is related to the increased risk of HNSCC in age ≤ 46 years (OR 1.56, p = 0.029). Rs157916, rs16873842, rs7801029, and rs7781295 exhibited an enhanced risk of HNSCC in men (OR 1.82, p = 0.004; OR 1.61, p = 0.028; OR 1.53, p = 0.047; OR 1.62, p = 0.021). Besides, we found that rs16873842 significantly increased the risk of Nasopharyngeal SCC (OR 4.04, p = 0.015). Rs157916 (OR 1.39, p = 0.028) and rs7781295 (OR 1.30, p = 0.028) had a high susceptibility to Thyroid SCC.Conclusions: This research indicated that polymorphisms in the LINC-PINT gene are significantly associated with an increased susceptibility to HNSCC, which suggest that LINC-PINT polymorphisms have a significant role in prevention and diagnosis of HNSCC.

Download Full-text

CORRELATION OF P21 EXPRESSION IN HEAD AND NECK SQUAMOUS CELL CARCINOMA WITH CLINICOPATHOLOGIC AND PROGNOSTIC PARAMETERS

Journal of Cancer & Allied Specialties ◽

10.37029/jcas.v1i2.33 ◽

2015 ◽

Vol 1 (2) ◽

Cited By ~ 1

Author(s):

Safana Sadaf ◽

Asif Loya ◽

Sajid Mushtaq ◽

Noreen Akhter ◽

Raza Hussain ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Survival Rate ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Tertiary Care ◽

Nodal Metastasis ◽

Neck Squamous Cell Carcinoma ◽

Depth Of Invasion ◽

Increased Risk

Purpose: Head and neck tumours include tumours of nose, paranasal sinuses, oropharynx, larynx and mouth. Squamous cell carcinoma (SCC) is the most common head and neck malignant tumour which accounts for 90% of head and neck malignant tumours. p21 is an important immunohistochemical marker which has signi cant role in predicting prognosis of head and neck SCC (HNSCC). Increased p21 expression in HNSCC is associated with bad prognosis in terms of increased risk of nodal metastasis, increased rate of recurrence and decreased survival rate. The purpose of this study was to evaluate the expression of p21 in HNSCC with various clinicopathologic and prognostic parametres. Materials and Methods: A total of 110 patients (n = 110) of HNSCC (oral cavity n = 98 and laryngeal tumours n = 12) were included in the study which were diagnosed and treated between January 2008 and January 2011 at a tertiary care centre in Pakistan. Mean age was 51 years (age range 15–78). 65 (59%) were male and 45 (41%) were female. Tumours were classi ed as p21 positive when ≥10% tumour cells were immunoreactive for p21. p21 expression was noted and correlated with T-stage, nodal metastasis, perineural and depth of invasion, recurrence and 2-year survival rate. Results: Of 110 cases, p21-positive cases were 88 (80%) compared to 22 (20%) negative. T1–T2 tumours with p21 expression were 59 (67.04%) while 17 cases (77.27%) had negative for p21 (P = 0.44). Amongst T3–T4, 29 cases showed p21 expression (32.96%) while 5 cases (22.73%) were negative (P = 0.44). Nodal metastasis was seen in 51 cases (57.95%) with p21 positivity as compared to 4 cases (18.8%) with no p21 expression (P = 0.0015). Perineural invasion was seen in 15 carcinomas (17.04%) having p21 positivity and 1 case (4.54%) with p21 negativity (P = 0.18). 48 cases (54.54%) had depth of invasion >1 cm with positive p21 as compared to 4 cases (18.18%) without (P value = 0.0035). 39 cases (44.31%) showed recurrence along with p21 expression while 3 cases (13.63%) showed recurrence without (P = 0.0076). 2-year survival rate was 56.81% (n = 88) in p21 positive cases, whereas it was 90.90% (n = 20) those with negative p21 (P = 0.0026). Conclusion: Positive p21 expression in HNSCC correlates with intermediate grade, late stage, increased nodal metastasis, tumour recurrence and decreased survival. p21 should be considered as an important prognostic and predictive marker in HNSCC to detect tumours at early stage and to improve therapy and prognosis. Key words: Head and neck squamous cell carcinoma, lymph node metastasis, p21, recurrence, survival rate

Download Full-text